Skip to main content
SpringerLink
Log in

Prostate Cancer Growth Inhibition by 1-(3,5-Dimethylphenyl)–6-methyl-1H-pyrazolo[4,3-c]pyridin-4(5H)-one via Down-regulation of Phosphorylation PI3K/AKT and STA3/JAK2

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
  • Published:
Doklady Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

In the present study, 1-(3,5-dimethylphenyl)-6-methyl-1H-pyrazolo[4,3-c]pyridin-4 (5H)-one (DPMPP) was investigated as an antiproliferative agent for prostate cancer cells and the mechanism of its action was studied. Cell lines 22Rv1 and SGC‑7901 were used as in vitro models of prostate cancer. The DPMPP treatment inhibited proliferation of 22Rv1 and SGC‑7901 cells in dose-depended manner. The viability of 22Rv1 and SGC‑7901 cells was reduced to 21 and 19%, respectively after treatment with 32 µM DPMPP. In DPMPP treated (16 µM) 22Rv1 and SGC‑7901 cells apoptosis increased to 62.78 and 68.51%, respectively. Moreover, DPMPP treatment caused cell cycle arrest in S phase and inhibition of PI3K/AKT activation. In the same time ROS production showed elevation and MMP (Matrix MetalloProteinase) decreased in the cells. Apparently DPMPP induces cytotoxicity through induction of oxidative response and apoptosis in prostate cancer cells in vitro. The PI3K/Akt/ERK phosphorylation was inhibited, while p21 and p53, death receptor, expression was promoted by DPMPP treatment. Therefore, DPMPP has a potential to be used as a therapeutic agent for treatment of prostate cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.
Fig. 8.

Similar content being viewed by others

REFERENCES

  1. Jemal, A., Siegel, R., and Xu, J.E., Ward Cancer statistics, 2010, Cancer J. Clin., 2010, vol. 60, pp. 277–300.

    Article  Google Scholar 

  2. Fedorov, A., Fluckiger, J., Ayers, G.D., Li, X., Gupta, S.N., Tempany, C., Mulkern, R., Yankeelov, T.E., and Fennessy, F.M., A comparison of two methods for estimating DCE-MRI parameters via individual and cohort based AIFs in prostate cancer: a step towards practical implementation, Magn. Reson. Imaging, 2014, vol. 32, pp. 321–329.

    Article  Google Scholar 

  3. Yu, E.Y., Massard, C., Gross, M.E., Carducci, M.A., Culine, S., Hudes, G., Posadas, E.M., Sternberg, C.N., Wilding, G., Trudel, G.C., et al., Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer, Urology, 2011, vol. 77, pp. 1166–1171.

    Article  Google Scholar 

  4. Shetty AV, Thirugnanam S, Dakshinamoorthy G, et al: 18a-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes, Int. J. Oncol., 2011, vol. 39, pp. 635–640.

    CAS  PubMed  Google Scholar 

  5. Maciej, D., Vishal, C.K., Valeria, N., Roberto, F., Kenji, S., Leonidas, E., Dominik, L., et al., Structure–activity relationship in pyrazolo[4,3-c]pyridines, first inhibitors of PEX14–PEX5 protein–protein interaction with trypanocidal activity, J. Med. Chem., 2020, vol. 63, pp. 847–879.

    Article  Google Scholar 

  6. Smyth, L.A., Matthews, T.P., Horton, P.N., Hursthouse, M.B., and Collins, I., Synthesis and reactivity of 3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones: development of a novel kinase-focused library, Tetrahedron, 2010, vol. 66, no. 15, pp. 2843–2854.

    Article  CAS  Google Scholar 

  7. Choi, Y.-M., Kim, H.-K., Shim, W., Anwar, M.A., Kwon, J.-W., Kwon, H.-K., et al., Mechanism of cisplatin-induced cytotoxicity is correlated to impaired metabolism due to mitochondrial ROS generation, PLoS One, 2015, vol. 10, no. 8. e0135083.

    Article  Google Scholar 

  8. Hamid, S.M., Cicek, S., Karamil, S., Ozturk, M.B., Debelec-Butuner, B., Erbaykent-Tepedelen, B., Varisli, L., Gonen-Korkmaz, C., Yorukoglu, K., and Korkmaz, K.S., HOXB13 contributes to G1/S and G2/M checkpoint controls in prostate, Mol. Cell Endocrinol., 2014, vol. 383, pp. 38–47.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Affiliated Jinan Third Hospital of Jining Medical University, Jining Medical University, 250132, Jinan, Shandong Province, China

    Jingxin Xue, Zhenwei Zhang & Heyi Hu

Authors
  1. Jingxin Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhenwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heyi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jingxin Xue.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xue, J., Zhang, Z. & Hu, H. Prostate Cancer Growth Inhibition by 1-(3,5-Dimethylphenyl)–6-methyl-1H-pyrazolo[4,3-c]pyridin-4(5H)-one via Down-regulation of Phosphorylation PI3K/AKT and STA3/JAK2. Dokl Biochem Biophys 495, 347–353 (2020). https://doi.org/10.1134/S160767292006006X

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S160767292006006X

Keywords:

Search

Navigation